p53 causes rapid SHP protein degradation independent of Mdm2.

<p>A: Western blots to determine the effects of p53 and Mdm2 on SHP protein expression in <i>p53^−/−Mdm2^−/−</i> MEF cells lacking p53 and Mdm2. The <i>p53^−/−Mdm2^−/−</i> MEF cells were transfected with Flag-SHP, Flag-p53 or Mdm2 expression vectors, and Mdm2, p53 or SHP proteins were detected using anti-Mdm2 and anti-Flag antibodies, as indicated. The sizes of p53 and SHP proteins are distinct, thus both proteins were detected simultaneously using anti-Flag antibodies on the same blot. B: Western blots to determine the effect of p53 on endogenous SHP protein expression. Flag-p53 expression vectors were transfected in HepG2 cells, and p53 (both endogenous and exogenous), SHP (endogenous), and Mdm2 (endogenous) proteins were detected using anti-p53, anti-SHP and anti-Mdm2 antibodies, respectively.